title: Breast cancer 1 (BRCA1) protein expression as a prognostic marker in sporadic epithelial ovarian carcinoma: an NCIC CTG OV.16 correlative study.
abstract: BACKGROUND
  Breast cancer 1 (BRCA1) protein inactivation in sporadic ovarian carcinoma (OC) is common and low BRCA1 expression is linked with platinum sensitivity. The clinical validation of BRCA1 as a prognostic marker in OC remains unresolved.
  
  
  METHODS
  In 251 patient samples from the NCIC CTG clinical trial, OV.16, BRCA1 protein expression was determined by immunohistochemistry.
  
  
  RESULTS
  For all patients, when BRCA1 score was analyzed as a continuous variable, there was no significant correlation between BRCA1 protein expression and progression-free survival (PFS) [adjusted hazard ratio (HR) = 1.15 (0.96-1.37), P = 0.12] or response rate [HR = 0.89 (0.70-1.12), P = 0.32]. In the 116 patients with minimal residual disease (RD), higher BRCA1 expression correlated significantly with worse PFS [HR = 1.40 (1.04-1.89), P = 0.03]. Subgroup analysis divided patients with minimal RD into low (BRCA1 ≤2.5) and high (BRCA1 >2.5) expression groups. Patients with low BRCA1 expression had a more favorable outcome [median PFS was 24.7 and 16.6 months in patients with low and high BRCA1, respectively; HR = 0.56 (0.35-0.89), P = 0.01].
  
  
  CONCLUSIONS
  This study suggests that BRCA1 protein is a prognostic marker in sporadic OC patients with minimal RD. Further research is needed to evaluate BRCA1 as a predictive biomarker and to target BRCA1 expression to enhance chemotherapeutic sensitivity.
authors.affiliation: Centre for Cancer Therapeutics, Ottawa Hospital Research Institute; The Division of Gynaecologic Oncology, The Ottawa Hospital, Ottawa. Electronic address: jweberpals@ottawahospital.on.ca.
authors.forename: J I
authors.initials: JI
authors.lastname: Weberpals
authors.affiliation: The NCIC Clinical Trials Group, Kingston.
authors.forename: D
authors.initials: D
authors.lastname: Tu
authors.affiliation: The NCIC Clinical Trials Group, Kingston.
authors.forename: J A
authors.initials: JA
authors.lastname: Squire
authors.affiliation: The Department of Pathology and Laboratory Medicine, The Ottawa Hospital, Ottawa.
authors.forename: M S
authors.initials: MS
authors.lastname: Amin
authors.affiliation: The Department of Pathology and Laboratory Medicine, The Ottawa Hospital, Ottawa.
authors.forename: S
authors.initials: S
authors.lastname: Islam
authors.affiliation: The Department of Pathology and Laboratory Medicine, The Ottawa Hospital, Ottawa.
authors.forename: L B
authors.initials: LB
authors.lastname: Pelletier
authors.affiliation: Centre for Cancer Therapeutics, Ottawa Hospital Research Institute.
authors.forename: A M
authors.initials: AM
authors.lastname: O'Brien
authors.affiliation: The BC Cancer Centre, Vancouver, Canada.
authors.forename: P J
authors.initials: PJ
authors.lastname: Hoskins
authors.affiliation: The NCIC Clinical Trials Group, Kingston.
authors.forename: E A
authors.initials: EA
authors.lastname: Eisenhauer
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019313:BRCA1 Protein / Q000096:biosynthesis* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D016190:Carboplatin / Q000008:administration & dosage; D000077216:Carcinoma, Ovarian Epithelial; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D019772:Topotecan / Q000008:administration & dosage
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D014408:Biomarkers, Tumor; D019772:Topotecan; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin